Abstract 3542
Background
Programmed cell death protein 6 (PDCD6) mediates apoptosis via p53 dependent and independent pathways and is implicated in many cancer hallmarks. A multi-omics analysis of colorectal cancer (CRC) cell lines identified PDCD6 as a candidate prognostic and predictive biomarker. PDCD6 is dysregulated in different cancers, but the role of PDCD6 in CRC is still poorly understood.
Methods
The clinicopathological data on 483 CRC patients treated at Mater Dei Hospital Malta between January 2008 and December 2011 were collated and tissue microarrays constructed in triplicate to represent central and peripheral tumour areas. PDCD6 protein expression was quantified by multiplex immunofluorescence (mIF; QuPath) along with fifteen other protein targets representing important cancer signalling and immune pathways. Expression of 770 genes was assessed using the NanoString nCounter® PanCancer Pathways Panel in a subset of 34 patients with low/high PDCD6 expression. Associations with clinicopathological parameters including disease-free survival and overall survival (OS) were calculated.
Results
Intra-tumoural PDCD6 protein expression was heterogeneous, having a higher expression at the tumour edge (p = 0.001). Invasive edge PDCD6 protein expression was significantly associated with TNM stage and tumour grade (p = 0.04 and <0.001, respectively), with lower PDCD6 expression in higher stage and poorly differentiated CRCs. PDCD6 expression was also associated with 5-year OS (p = 0.003), and higher PDCD6 expression revealed a trend towards longer OS. PDCD6 and Ki67 expression were negatively correlated (rs = - 0.192, p = 0.002). Low and high PDCD6 expressers showed differential gene expression in several other cancer pathways.
Conclusions
PDCD6 shows both inter- and intra-tumoural heterogeneity in CRC, with expression patterns consistent with a tumour suppressive function. Contrarily, wider literature suggests that PDCD6 might also have an intrinsic oncogenic role under certain circumstances, and further exploration of PDCD6 pleiotropism in CRC is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Romina Briffa.
Funding
REACH HIGH Scholars Programme Part-financed by the European Union, Operational Programme II; Cohesion Policy 2014-2020 "Investing in human capital to create more opportunities and promote the wellbeing of society.".
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2108 - Biomarker analyses of ramucirumab in patients with platinum refractory urothelial cancer from RANGE, a global, randomized, double-blind, phase 3 study.
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3090 - Comparison of Immuno-Oncology (IO) Biomarkers in Adenocarcinoma (ACB), Urothelial Carcinoma (UCB) and Squamous Cell Carcinoma (SCCB) of the Bladder, with interim results from PURE01
Presenter: Daniele Raggi
Session: Poster Display session 3
Resources:
Abstract
5211 - Potential role of a clinical, taxonomical classification and RNA expression integrated signature to predict response to neoadjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC) patients
Presenter: Albert Font
Session: Poster Display session 3
Resources:
Abstract
3206 - Hyperphosphatemia due to Erdafitinib (a Pan-FGFR Inhibitor) and Anti-tumor Activity Among Patients (Pts) with Advanced Urothelial Carcinoma (UC)
Presenter: Scott Tagawa
Session: Poster Display session 3
Resources:
Abstract
3110 - Prognostic role of FGFR Mutations and FGFR mRNA expression in metastatic urothelial cancer treated with anti-PD(L1) inhibitors in first and second line setting
Presenter: Florian Roghmann
Session: Poster Display session 3
Resources:
Abstract
3564 - Circulating tumour DNA (ctDNA) utility as a biomarker for metastatic urothelial carcinoma (mUC)
Presenter: Jean-Michel Lavoie
Session: Poster Display session 3
Resources:
Abstract
2760 - Comparative analysis of tumor mutational burden (TMB) prediction methods and its association with determinants of the tumor immune microenvironment of urothelial bladder cancer (UBC)
Presenter: Markus Eckstein
Session: Poster Display session 3
Resources:
Abstract
2513 - The Immunoscore in patients with urothelial carcinoma treated with neoadjuvant chemotherapy: clinical significance for pathological response and survival
Presenter: Elise Nassif
Session: Poster Display session 3
Resources:
Abstract
2835 - Genomic analysis of urothelial cancer and associations with treatment choice and outcome
Presenter: David Sarid
Session: Poster Display session 3
Resources:
Abstract
5763 - cfDNA is an acceptable but insufficient means of characterizing FGFR3 mutation in patients with metastatic urothelial cancer (mUC)
Presenter: Sumanta Pal
Session: Poster Display session 3
Resources:
Abstract